TNF and Respiratory insufficiency due to muscle weakness: Glial activation has been demonstrated to oppose opioid analgesia and enhance opioid tolerance, dependence, reward and respiratory depression by upregulating the production of proinflammatory cytokines (TNFα, IL-1), pain-relevant neurotransmitters from sensory afferent terminals and the number and/or conductivity of AMPA and NMDA glutamate receptors [33-35].